Dysbiosis involving methionine and PPAR-γ pathwaysis associated with early onset atopic dermatitis and food allergy

Anchalee Senavonge,^1,2* Massalin Nakphaichit,^3,4* Wanwipa Vongsangnak,^5,6 Sittiruk Roytrakul,⁷ Preecha Patumcharoenpol,⁵ Amornthep Kingkaw,⁸ Chantha Wongoutong,⁹ Wanlapa Weerapakorn,¹ Natapol Pornputtapong,^10,11 Orawan La-ongkham,¹² Yong Poovorawan,¹³ Nasamon Wanlapakorn,¹³ Pannipa Kittipongpattana,¹ Sunee Nitisinprasert,^3,4 Pantipa Chatchatee,¹ Narissara Suratannon¹

Affiliations:
¹ Center of Excellence for Allergy and Clinical Immunology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
² BNH Asthma and Allergy center, BNH Hospital, Bangkok, Thailand
³ Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, Thailand
⁴ Center of Excellence for Microbiota Innovation, Kasetsart University, Bangkok, Thailand
⁵ Department of Zoology, Faculty of Science, Kasetsart University, Bangkok, Thailand
⁶ Omics Center for Agriculture, Bioresources, Food, and Health, Kasetsart University (OmiKU), Bangkok, Thailand
⁷ Functional Proteomics Technology Laboratory, Functional Ingredients and Food Innovation Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand
⁸ Interdisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok, Thailand
⁹ Department of Statistics, Faculty of Science, Kasetsart University, Bangkok, Thailand
¹⁰ Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
¹¹ Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
¹² Department of Applied Microbiology, Institute of Food Research and Product Development, Kasetsart University, Bangkok, Thailand
¹³ Center of excellence in clinical virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

*These authors shared position of the first author

Abstract

Background: Atopic dermatitis (AD) and food allergy (FA) often originate early in life. Gut microbiota interactions with the host immune system influence allergy development, yet the distinct gut microbiome and functional profiles in individuals with AD, FA, or both AD+FA remain underexplored.
Objective: We investigated microbial colonization and proteomic profiles in infants with AD, FA, and AD+FA compared to age- and sex-matched controls from the Allergy Development in Early Life and Associated Factors in the Thai Birth Cohort (ALICE).
Methods: Gut microbiomes from stool samples were analyzed using 16S sequencing, and proteomic analysis was conducted by liquid chromatography–tandem mass spectrometry.
Results: The study included 16 AD, 5 FA, 5 AD+FA subjects, and 26 controls. AD+FA group exhibited the most severe dysbiosis. Enrichment of proteins involved in methionine biosynthesis in Bifidobacterium scardovii and high Erysipelotrichaceae colonization suggest a link to high-fat diets, known to reduce intestinal short-chain fatty acid and serotonin levels, contributing to allergies. Erysipelotrichaceae in AD+FA groups also expressed proteins related to histidine degradation. Low Bifidobacteriaceae levels were noted in FA and AD+FA, with more pathogenic strains colonized. Increased Bacteroidaceae in FA and AD+FA and Enterobacteriaceae in FA were detected. Pathways involving vitamin B1, a ligand for proliferator-activated receptor-γ (PPAR-γ) from Enterobacteriaceae could promote TH2 cells, type 2 innate lymphoid cells, and M2 macrophages, likely contribute to allergic inflammation.
Conclusion: AD+FA phenotype exhibited the most distinctive gut microbiome alterations, highlighting unique dysbiosis patterns. Microbiome biosynthesis pathways involving metabolism of methionine, histidine, serotonin, and vitamin B1 point to new targets for modifying or treating AD and FA.
Key words: proteomics, gastrointestinal microbiome, cohort studies, dermatitis, atopic, food hypersensitivity, methionine, PPAR-γ, vitamin B1